The present application relates to isolating ions in a quadrupole ion trap.
Quadrupole ion traps are used in mass spectrometers to store ions that have mass-to-charge ratios (m/z—where m is the mass and z is the number of elemental charges) within some predefined range. In the ion trap, the stored ions can be manipulated. For example, ions having particular mass-to-charge ratios can be isolated or fragmented. The ions can also be selectively ejected or otherwise eliminated from the ion trap based on their mass-to-charge ratios to a detector to create a mass spectrum. The stored ions can also be extracted, transferred or ejected into an associated tandem mass analyzer such as a Fourier Transform, RF Quadrupole Analyzer, Time of Flight Analyzer or a second Quadrupole Ion Trap Analyzer.
All ion traps have limitations in how many ions can be stored or manipulated efficiently. In addition, obtaining structural information of a particular ion can also require that ions having a particular m/z (or m/z's) be selectively isolated in the ion trap and all other ions be eliminated from the ion trap. In an MS/MS experiment, the isolated ions are subsequently fragmented into product ions that are analyzed to obtain the structural information of the particular ion. Thus, there are several reasons for efficient ion isolation techniques in ion trapping instruments.
Quadrupole ion traps use substantially quadrupole fields to trap the ions. In pure quadrupole fields, the motion of the ions is described mathematically by the solutions to a second order differential equation called the Mathieu equation. Solutions can be developed for a general case that applies to all radio frequency (RF) and direct current (DC) quadrupole devices including both two-dimensional and three-dimensional quadrupole ion traps. A two dimensional quadrupole trap is described in U.S. Pat. No. 5,420,425, and a three-dimensional quadrupole trap is described in U.S. Pat. No. 4,540,884, both of which are incorporated in their entirety by reference.
In general, solutions to the Mathieu equation and corresponding motion of the ions are characterized by reduced parameters au and qu where u represents an x, y, or z spatial direction that corresponds to the displacement along the axis of symmetry of the field.au=(KaeU)/(mro2ω2) qu=(KqeV)/(mro2ω2)
where:
V=Amplitude of the applied radio frequency (RF) sinusoidal voltage
U=Amplitude of the applied direct current (DC) voltage
e charge on the ion
m=mass of the ion
ro=device characteristic dimension
ω=2πf
f=frequency of RF voltage
Ka=device-field geometry dependent constant for au 
Kq=device-field geometry dependent constant for qu 
The RF voltage generates an RF quadrupole field that works to confine the ions' motion to within the device. This motion is characterized by characteristic frequencies (also called primary frequencies) and additional, higher order frequencies and these characteristic frequencies depend on the mass and charge of the ion. A separate characteristic frequency is also associated with each dimension in which the quadrupole field acts. Thus separate axial (z dimension) and radial (x and y dimensions) characteristic frequencies are specified for a 3-dimensional quadrupole ion trap. In a 2-dimensional quadrupole ion trap, the ions have separate characteristic frequencies in x and y dimensions. For a particular ion, the particular characteristic frequencies depend not only on the mass of the ion, the charge on the ion, but also on several parameters of the trapping field.
An ion's motion can be excited by resonating the ion at one or more of their characteristic frequencies using a supplementary AC field. The supplementary AC field is superposed on the main quadrupole field by applying a relatively small oscillating (AC) potential to the appropriate electrodes. To excite ions having a particular m/z, the supplementary AC field includes a component that oscillates at or near the characteristic frequency of the ions' motion. If ions having more than one m/z are to be excited, the supplementary field can contain multiple frequency components that oscillate with respective characteristic frequencies of each m/z to be resonated.
To generate the supplementary AC field, a supplementary waveform is generated by a waveform generator, and the voltage associated with the generated waveform is applied to the appropriate electrodes by a transformer. The supplementary waveform can contain any number of frequency components that are added together with some relative phase. These waveforms are hereon referred to as a resonance ejection frequency waveform or simply an ejection frequency waveform. These ejection frequency waveforms can be used to resonantly eject a range of unwanted ions from the ion trap.
When an ion is driven by a supplementary field that includes a component whose oscillation frequency is close to the ion's characteristic frequency, the ion gains kinetic energy from the field. If sufficient kinetic energy is coupled to the ion, its oscillation amplitude can exceed the confines of the ion trap. The ion will subsequently impinge on the wall of the trap or will be ejected from the ion trap if an appropriate aperture exists.
Because different m/z ions have different characteristic frequencies, the oscillation amplitude of the different m/z ions can be selectively determined by exciting the ion trap. This selective manipulation of the oscillation amplitude can be used to remove unwanted ions at any time from the trap. For example, an ejection frequency waveform can be utilized to isolate a narrow range of m/z ratios during ion accumulation when the trap is first filled with ions. In this way the trap may be filled with only the ions of interest, thus allowing a desired m/z ratio to be detected with enhanced signal-to-noise ratio. Also a specific m/z range can be isolated within the ion trap either after filling the trap for performing an MS/MS experiment or after each dissociation stage in MSn experiments.
Ion isolation can be performed using broadband resonance ejection frequency waveforms that are typically created by summing discrete frequency components represented by sine waves (as described in U.S. Pat. No. 5,324,939). That is, the summed sine waves have discrete frequencies corresponding to the m/z range of ions that one desires to eject but excluding frequency components corresponding to the m/z range of ions that one desires to retain. The omitted frequencies define a frequency notch in the ejection frequency waveform. Thus when the ejection frequency waveform is applied, ions having undesired m/z's can be essentially simultaneously ejected or otherwise eliminated while the desired m/z ions are retained, because their m/z ratio values correspond to where the frequency components are missing from the ejection waveform.
To eject or otherwise eliminate all undesired ions substantially simultaneously, the ejection frequency waveform needs to include closely spaced discrete frequency components. Thus the ejection frequency waveform is typically generated from a large number of sine waves. In general, controlling such waveform generation is a complex problem. The general problem can be simplified if the discrete frequencies of the sine waves are spaced uniformly, and each sine wave has the same relative amplitude.
To further simplify the waveform generation, the discrete frequencies may be relatively widely separated (spaced, for example, at least 1500 Hz apart), and the system can include a means to modulate the RF voltage to cause ions that would otherwise fall between frequency components to come into resonance (see, e.g. U.S. Pat. No. 5,457,315).
When it is desirable to isolate a m/z range whose width is substantially less that 1 amu (atomic mass unit, which is 1.660538×10 −27 kilograms), the broadband ejection frequency waveforms may require many frequency components that are spaced so closely that waveform generation becomes impractical. Such a waveform if utilized would, in addition, have to be applied for an impractically long time. For example with an RF frequency of 760 kHz, obtaining even unit resolution isolation is difficult above m/z 1200 using 500 Hz spacing. In an alternative technique, the supplementary field includes only a single frequency component, and the undesired ions are ejected by slowly increasing or decreasing the amplitude of the trapping RF voltage (see Schwartz, J. C.; Jardine, I. Rapid Comm. Mass Spectrum. 6 1992 313).